Australia opener David Warner has been ruled out of the Boxing Day Test, while Sean Abbott will also miss the Melbourne date with India.
Warner will sit out the blockbuster clash as he continues to recover from a groin injury, which sidelined him for the opening Test in Adelaide, where Australia won by eight wickets.
The 34-year-old Warner suffered an adductor injury during the second ODI against India last month as he watched Australia humble the tourists in the day-night contest at Adelaide Oval.
Australia paceman Abbott has returned to full fitness, but he will also be absent for the second Test due to Cricket Australia's (CA) strict biosecurity protocols amid the coronavirus pandemic.
Warner and Abbott both departed for Melbourne on Saturday as a COVID-19 outbreak moves through Sydney, though they will be unable to enter the squad's hub.
"David Warner and Sean Abbott will re-join the Australian men's Test squad ahead of the third Test against India," a CA spokesman said.
"Warner and Abbott spent time in Sydney outside the team's bio-secure hub to recover from injury. While neither player has been in a specific 'hotspot' as outlined by NSW Health, Cricket Australia's biosecurity protocols do not allow them to re-join the squad in time for the Boxing Day Test.
"Warner has not fully recovered from a groin injury suffered in the ODI Series against India and would not have been available for the second Test match, while Abbott has recovered from a calf strain sustained during Australia A's tour match against India and would have been available for selection for the Boxing Day Test.
"The pair travelled from Sydney to Melbourne to continue their rehabilitation given the changing public health situation in Sydney at the time."
Matthew Wade and Joe Burns opened the batting for Australia in the first Test against India, and the pair are in line to continue atop the order.
Wade (33) and Burns (51 not out) put on a 70-run stand as Australia embarrassed Virat Kohli's India, who were held to a record-low Test score of 36 in the second innings.
The Boxing Day matchup will be the 100th men's Test between Australia and India, just the seventh fixture in the game's history to reach a century of iterations – Australia have won 43 of their previous 99 Tests against India (D27, L28).
Steve Smith (1,431) needs just 69 runs to become the fifth Australia player to reach 1,500 Test runs against India. His batting average of 79.5 from his 22 innings is the highest of any Australian to have logged more than six innings against them.
Australia spinner Nathan Lyon requires nine more wickets to reach 400 in Test cricket – only Shane Warne (708) and Glenn McGrath (563) have taken more for Australia in the men's format.